Cannabis sativa, a globally distributed herbaceous plant, is the most widely used drug, with 3.9% of the world’s population consuming it for recreational and medical purposes, a trend increased by the COVID-19 pandemic. Despite being marketed as harmless, its consumption is linked to intoxication, contamination, and allergies. C. sativa contains over 400 components, including 60 cannabinoids affecting the central nervous and immune systems. The primary psychoactive cannabinoids are tetrahydrocannabinol (THC) and cannabidiol (CBD). Intoxication can be chronic from prolonged use or acute from excessive THC consumption, causing symptoms like irritability, disorientation, hallucinations, and various physical effects. Allergies to Cannabis are becoming more relevant, though prevalence is underestimated due to illegality and lack of reliable diagnostic methods. Allergic reactions include rhinoconjunctivitis, asthma, dermatitis, and anaphylaxis. Legalization in several countries is expected to increase intoxication and hypersensitivity cases, complicating clinical differentiation and management. THC induces sedative, hallucinogenic, and stimulant effects, metabolized mainly in the liver and posing risks to infants via placenta and breast milk. CBD, with anti-inflammatory properties, is also metabolized in the liver. Excessive or constant marijuana consumption can cause toxicity, with symptoms varying by age and duration of exposure. Cannabis allergens can cross-react with other plant-derived foods, causing symptoms in sensitized individuals. Diagnosing cannabis allergy relies on patient history and skin prick tests (SPT), but the scarcity of extracts and legal restrictions poses challenges. Cell-based tests like basophil activation (BAT) and mast cell activation (pMAT) can enhance diagnostic accuracy. Further studies are needed to confirm the allergenic potential of cannabis and to develop better diagnostic and management strategies for associated intoxications and allergies.